Abstract

The identification of lung tumor-initiating cells and associated markers may be useful for optimization of therapeutic approaches and to provide predictive and prognostic information in lung cancer patients. CD133, a surface glycoprotein linked to organ-specific stem cells was described as marker of cancer-initiating cells in different tumor types. Here we report that a CD133+ESA+population is enriched in primary non-small cell lung cancer (NSCLC) compared to normal lung tissue and has higher tumorigenic potential and increased expression of genes involved in stemness, adhesion, motility and drug efflux than the CD133- counterpart. Cisplatin treatment of lung cancer cells in vitro resulted in enrichment of CD133+ fraction after acute cytotoxic exposure and in cells with stable cisplatin resistant phenotype. Subpopulations of CD133+ ABCG2+ and CD133+CXCR4+ cells were spared by in vivo cisplatin treatment of lung tumor xenografts and restored the tumor after chemotherapy cessation. CD133 expression was positively correlated with resistance to platinum-containing regimens in advanced stage NSCLC patients. Our results indicate that chemoresistant populations with highly tumorigenic and stem-like features are present in lung tumors. The molecular features of these cells may provide the rationale for more specific therapeutic targeting and for defining predictive factors in clinical management of this lethal disease.